Immunological tolerance to a hapten. I. Induction and maintenance of tolerance to trinitrophenyl with trinitrobenzene sulfonic acid.

Treatment of mice with a nonimmunogenic preparation of free reactive hapten, trinitrobenzene sulfonic acid (TNBS), leads to the induction of a state of tolerance to the hapten, 2,4,6-trinitrophenyl (TNP). This is determined by the lack of response to the haptenic moiety in an immunogenic hapten-carrier conjugate (TNP-SRBC) as assayed both by serum antibody titrations and the hemolytic plaque assay. The tolerance produced is specific for the hapten, since the anticarrier responses are essentially unaltered compared with the control values. The unresponsiveness induced by TNBS treatment is a dose-dependent phenomenon, becoming less complete at lower doses of TNBS. The tolerance is of a definite length, both in its induction phase and in the duration of the established unresponsive state. Tolerance can be maintained and extended, and may also be reentered once escape has been initiated.